The structure of human 5-lipoxygenase

NC Gilbert, SG Bartlett, MT Waight, DB Neau… - Science, 2011 - science.org
NC Gilbert, SG Bartlett, MT Waight, DB Neau, WE Boeglin, AR Brash, ME Newcomer
Science, 2011science.org
The synthesis of both proinflammatory leukotrienes and anti-inflammatory lipoxins requires
the enzyme 5-lipoxygenase (5-LOX). 5-LOX activity is short-lived, apparently in part because
of an intrinsic instability of the enzyme. We identified a 5-LOX–specific destabilizing
sequence that is involved in orienting the carboxyl terminus, which binds the catalytic iron.
Here, we report the crystal structure at 2.4 angstrom resolution of human 5-LOX stabilized by
replacement of this sequence.
The synthesis of both proinflammatory leukotrienes and anti-inflammatory lipoxins requires the enzyme 5-lipoxygenase (5-LOX). 5-LOX activity is short-lived, apparently in part because of an intrinsic instability of the enzyme. We identified a 5-LOX–specific destabilizing sequence that is involved in orienting the carboxyl terminus, which binds the catalytic iron. Here, we report the crystal structure at 2.4 angstrom resolution of human 5-LOX stabilized by replacement of this sequence.
AAAS